26: Neurodegenerative Disorders

Question 1

Two things aggregates of misfolded proteins cause

Answer 1

1. Gain of toxicity

2. Loss of biological function

Question 2

Neurodegenerative diseases

Answer 2

Large group of neurological disorders primarily affecting neurons, with heterogeneous clinical and pathological expression

Question 3

Common denominator of neurodegenerative disorders

Answer 3

Misfolded proteins

Question 4

Familial vs sporadic neurodegenerative disorders

Answer 4

Familial: mutations in specific genes; early onset forms of disease
Sporadic: usually due to brain aging/random mutation; represent late onset of disease

Question 5

Most common neurodegenerative disorder + most common form of dementia

Answer 5

Alzheimer’s

Question 6

Extracellular vs intracellular deposits in Alzheimer’s

Answer 6

Extracellular: AB misfolding -> insoluble plaques in the brain
Intracellular: tau proteins are hyperphosphorylated -> form neurofibrillary tangles

Question 7

Treatment for Parkinson’s

Answer 7

Symptomatic treatment; dopamine replacement therapy, deep brain stimulation, surgery

Question 8

Role of Htt protein

Answer 8

Development of brain neurons before birth, signaling, transport, protecting cell from apoptosis, possible role in DNA repair

Question 9

HTT gene normal amount of trinucleotide repeats

Answer 9

10-35 CAG repeats is normal

Question 10

What does CAG code for? What does it form?

Answer 10

CAG = glutamine; with lots of repeats, the polyglutamine structure forms intramolecular H bonds -> misfolding and aggregation